The present invention relates to a method of detecting cancer and, more particularly, to methods of optimizing drug treatment for cancer.
Cancer is responsible for the majority of morbidity and mortality worldwide, despite recent advances in medical technology. Current therapeutic strategies focus predominantly on achieving the removal or death of cancer cells within the patient, through a diverse array of surgical and non-surgical techniques; the most widely used are chemotherapy and gamma irradiation. Those methods have a number of prominent disadvantages, in particular the culling of healthy cells/tissues within the patient, and the rather toxic side-effects of the current generation of chemotherapeutic drugs utilized in cancer treatment.
‘Differentiation therapy’ is an alternative approach which promotes reversion of phenotype from malignant to normal. Differentiation therapy is based on the concept that cancer cells are normal cells that have been arrested at an immature or less differentiated state, lack the ability to control their own growth, and thus multiply at an abnormally fast rate. Differentiation therapy aims to force the cancer cell to resume the process of maturation. Although differentiation therapy does not kill the cancer cells, it restrains their growth and allows the application of more conventional therapies (such as chemotherapy) to eradicate the remaining malignant cells.
Differentiation therapy has a number of advantages over conventional therapeutic strategies that target death of cancer/tumor cells. For a start, the culling of healthy cells/tissues within the patient with chemotherapeutic drugs or gamma irradiation would be eliminated, together with their associated adverse side-effects. In many cases, the killing of cancer cells through gamma irradiation or chemotherapeutic eliminates most, but not completely all cancer cells within the patient, thereby leading to remission of the disease. With differentiation therapy, it is speculated that by inducing some of the cancer cells into the pathway of terminal differentiation and eventual senescence, this would somehow signal other cancer cells to follow suit through a variety of mechanisms.
Various markers have been used as a means of monitoring patients undergoing differentiation therapy. One such marker is alkaline phosphatase, wherein expression of same was shown to correlate with the differentiation status of a cell [Patnaik A, et al., Clin. Can Research, 2002 July; 8(7):2142-8; Rephaeli A, Zhuk R, Nudelman A, 2000, Drug Develop. Res. Vol 50:379-391].
Rapid and easy detection of such markers with high sensitivity, selectivity and accuracy paves the way for tailoring therapeutic agent to specific patients—‘personalized medicine’. This is of great importance in cancer therapy where it is now known that tumor treatment response cannot be predicted only from its type and anatomical location.
Until presently, there is no detection system for such markers which meets all these demands.
U.S. Pat. App. No. 20060100488 teaches detection of cancerous cells by directly monitoring the electrical response of the cells following application of an alternating current. WO 91/15595 teaches analysis of electrical conductivity of cancer cells for monitoring responsiveness to therapy and drug screening. Specifically, WO 91/15595 teaches monitoring the effectiveness of a particular agent to inhibit increases in the volume and number of cancer cells by analyzing electrical conductivity thereof. Accordingly, both these patent applications teach that the intrinsic electrical properties of a cancer cell may be used as markers for detection and monitoring of cancer cells.
U.S. Pat. Appl. No. 20040053425 teaches amperometric analysis of an analyte in a fluid, wherein the electrode comprises the current producing enzyme. U.S. Pat. Appl No. 20040053425 does not teach amperometric detection of intracellular markers.
U.S. Pat. No. 5,149,629, teaches amperometric analysis of markers, including cancer cell markers, wherein the electrode comprises antibodies capable of binding the markers thereto. The analysis is by substrate competition. U.S. Pat. No. 5,149,629 does not detect endogenous amperometric features of cancer cells.
Thus, amperometric detection of analytes has been shown to be an effective method for detection. However, until presently, amperometric detection has not been used for analyzing cellular enzymatic activities.